This invention relates to novel 2-oxo-1-azetidine sulfonic acid derivatives which are of value for use in combination with .beta.-lactam antibiotics to increase their effectiveness in infection caused by .beta.-lactamase producing bacteria.
Of the commercially available .beta.-lactam antibiotics, penicillins and cephalosporins are best known and frequently used. Although widely used as useful chemotherapeutic agents, enzymatic inactivation of .beta.-lactam antimicrobial agents has been an obstacle to the treatment of infection for as long as these agents have been used. The production of enzymes that degrade the .beta.-lactam containing antimicrobial agents--penicillins and cephalosporins--is an important mechanism of bacterial resistance, thereby causing the antibiotic to lose it's antimicrobial activity. A novel approach to countering these bacterial enzymes is the delivery of a .beta.-lactam antimicrobial agent together with an enzyme inhibitor. When a .beta.-lactamase inhibitor is used in combination with a .beta.-lactam antibiotic, it can increase or enhance the antibacterial effectiveness of the antibiotic against certain microorganisms.
The present invention provides certain novel 2-oxo-1-azetidine sulfonic acid derivatives which are potent inhibitors of bacterial .beta.-lactamases, particularly against class C .beta.-lactamases (cephalosporinase). Aztreonam (U.S. Pat. No. 4,775,670) is a known monobactam antibiotic. Several publications (e.g., Antimicrobial Agents of Chemotherapy, vol. 22, pp. 414-420, 1982; Chemotherapy, vol. 30, pp. 398-407 (1984); J. Antibiotics, vol. 35, no. 5, pp. 589-593 (1982); J. Antibiotics, vol. 43, no. 4, pp. 403-410 (1990)! suggest that aztreonam possesses .beta.-lactamase inhibitory properties.